Lower Plasma Glucose Concentrations Research Articles

Neonatal Hypoglycemia.

Neonatal hypoglycemia (NH) is broadly defined as a low plasma glucose concentration that elicits hypoglycemia-induced impaired brain function. To date, no universally accepted threshold (reference range) for plasma glucose levels in newborns has been published, as data consistently indicate that neurologic responses to hypoglycemia differ at various plasma glucose concentrations. Infants at risk for NH include infants of diabetic mothers, small or large for gestational age, and premature infants. Common manifestations include jitteriness, poor feeding, irritability, and encephalopathy. Neurodevelopmental morbidities associated with NH include cognitive and motor delays, cerebral palsy, vision and hearing impairment, and poor school performance. This article offers a timely discussion of the state of the science of NH and recommendations for neonatal providers focused on early identification and disease prevention.

A potential role for GPR107 in the development of Hypoglycemia Unawareness

Diabetes remains one of the largest health burdens in modern society and while an estimated 37.3 million people suffer from either type 1 or type 2 diabetes worldwide, a further 96 million people are currently estimated to be prediabetic. So far, most efforts for diabetic therapies have been focused on insulin-replacement therapies and secretagogues; however, a common risk associated with these therapies is hypoglycemia. Hypoglycemia is defined as low plasma glucose levels (< 70 mg/dl) and can lead to loss of consciousness and death. Recently, it has been established that repeated exposure to bouts of hypoglycemia in diabetic individuals likely impairs sympathoadrenal counter regulation, and shifts the glycemic threshold for symptoms to lower plasma glucose concentrations, close to levels which result in cognitive failure. This pathology has been titled hypoglycemia unawareness (HU) and constitutes a major risk factor for developing severe hypoglycemia. The development of severe hypoglycemia in diabetics accounts for a six-fold increase in mortality, compared to diabetic individuals who do not experience severe hypoglycemia. Thus, it is important to understand how to prevent and reverse its development. We have developed a novel rat model of HU in which rats are exposed to insulin-induced recurrent hypoglycemia for five consecutive days. In this model of HU, we found that GPR107 expression is dramatically increased in the hypothalamus of rats exhibiting loss of hypoglycemia-induced food intake. Our group previously identified GPR107 as a receptor for neuronostatin (NST), a 13 amino acid peptide derived from the somatostatin prepro-hormone, which can exert anorexigenic actions in the hypothalamus. Using a GPR107-flox rat model we are currently evaluating the effect of hypothalamic knock-down of GPR107 on the development of HU and basal feeding behavior. We anticipate that if knock-down of GPR107 reverses HU, the development of NST antagonists could potentially be useful therapeutically for diabetic patients who experience recurrent hypoglycemia. Our GPR107-flox rat model will enable us to identify upstream and downstream interacting partners of GPR107/NST. This could reveal hypothalamic pathways involved in the development of HU that also could serve as potential therapeutic targets for this devastation consequence of iatrogenic hypoglycemia. Internal Funds St. Louis University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Relationship between Neonatal Cerebral Fuels and Neurosensory Outcomes at 3 Years in Well Babies: Follow-Up of the Glucose in Well Babies (GLOW) Study

Plain Language SummaryIn the Glucose in Well babies and their later Neurodevelopment (GLOWiNg) study, we investigated whether the availability of brain fuels in healthy term babies during the first 5 days after birth was associated with their neurodevelopmental progress at 3 years of age. We had measured plasma glucose, lactate, and beta-hydroxybutyrate concentrations when the children were babies, as these are the most common brain fuels. We used the Ages and Stages questionnaire, which is completed by parents, to assess the child’s development in areas including communication, motor skills (fine and gross), and problem solving.We studied 64 families whose babies were part of the Glucose in Well Babies (GLOW) study in New Zealand. Using both structural equation modelling and linear regression, we found that even though many babies experienced episodes of low plasma glucose concentrations, there was no detectable relationship between these episodes and developmental progress at 3 years of age. We explored other factors, including glucose concentrations, total fuels available, and the duration of low glucose episodes, and found no significant associations. Our results suggest that in healthy term babies, episodes of low glucose concentrations in the first days after birth may be part of the normal metabolic transition after birth and may not have long-term implications for neurodevelopment. However, larger studies using different assessment tools are needed to confirm these findings.

Knowledge, Attitude and Practice of Diabetic Patients About Symptoms of Hypoglycaemia in Atbara Teaching Hospital, December 2022 – October 2023

Introduction: Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia, which can increase the risk of micro and macro vascular complications. Hypoglycemia strongly associated with increase mortality in diabetic patients. The American Diabetes Association defines the hypoglycaemia as “any abnormally low plasma glucose concentration that exposes the subject to potential harm”, and proposes a threshold of <70 mg/dl. Prevention of hypoglycaemia can occur if much efforts spent in patient education regarding risk factors, food & physical activity, warning signs, and treatment of hypoglycaemia at an early stage. Objective: To identify Knowledge, Attitude and Practice of Diabetic patients about symptoms of Hypoglycaemia at Atbara teaching hospital. Method: A descriptive cross-sectional hospital-based study done in Atbara teaching hospital, River Nile state, Sudan. From December 2022 – October 2023. The study population were all diabetic patients who presented to the hospital during the period of the study. Exclusion criteria was severely ill patient or those who refuse to participate in the study. With total coverage sample size was 200. The data was collected by interviewing the respondents through close ended questionnaire. The collected data was analyzed by using SPSS. Result: The male to female ratio equal one. With the predominant age between 20 to 35. Most of the participants HBA1c were between 7%-10%. The duration of diabetes was not exceeding 10 years in 44% of the participants. Majority were on oral hypoglycemic drugs with good adherence to it. Tremor is the most reported symptoms of hypoglycemia. With most of the participants deal with the symptoms by them self. Conclusion: Over all the participants show acceptable level of knowledge toward hypoglycemia. Expressed through that most of them deal with the symptoms immediately by them self. Attitude of the participant need to be more investigated in the future with further studies.

Efficacy of nutritional selenium nanoparticles on growth performance, immune response, antioxidant capacity, expression of growth and immune-related genes, and post-stress recovery in juvenile Sobaity seabream (Sparidentex hasta)

This study evaluated the impacts of nano-Se on the growth, immunity, antioxidant capacity, physiological parameters, gene expression, and stress resistance of fingerling Sobaity seabream (Sparidentex hasta). The fish with an average weight of 21.5 ± 0.1 g were divided into four treatment groups in triplicates that received one of the test diets supplemented with varying levels of nano-Se: 0 (control), 0.5 (Se-0.5), 1 (Se-1), and 2 (Se-2) mg/Kg for 60 days. The results showed that final weight, weight gain rate, specific growth rate, feed intake, and feed conversion ratio improved with significant linear and quadratic trends (P < 0.05) in response to nano-Se-supplemented diets, and the best values were measured in the Se-2 group. Superoxide dismutase activity level remained unaffected among the four groups (P > 0.05). Catalase activity increased in nano-Se-supplemented groups, with the highest level measured in fish fed the Se-0.5 diet. Glutathione peroxidase activity levels were not significantly different between the control and nano-Se groups, but the lowest malondialdehyde concentration was detected in the Se-2 group. Nano-Se had no marked effect on total plasma Ig levels; however, the highest lysozyme activity and alternative complement activity (ACH50) were observed in the Se-0.5 and Se-2 groups, respectively. No significant differences (P > 0.05) were observed in plasma total protein, albumin, globulin, triglyceride, and thyroid hormone (T3 and T4) contents among the groups. However, the lowest cholesterol and low-density lipoprotein values and the highest high-density lipoprotein concentration were measured in the Se-2 group. The Se-0.5 and Se-1 groups exhibited significantly lower levels of aspartate aminotransferase activity, and the lowest alkaline phosphatase activity level was detected in the Se-1 group. The expression level of insulin-like growth factor I gene in all nano-Se-fed groups was significantly higher than the control. Also, the expression of interleukin-1β and lysozyme genes was significantly upregulated in nano-Se-supplemented groups, with the highest values in the Se-2 group. Following acute crowding stress, plasma cortisol and lactate levels at all post-stress time intervals were not significantly different among the experimental groups. Fish fed the Se-0.5 and Se-2 diets tended to have lower plasma glucose concentrations than other groups. In conclusion, dietary nano-Se at 2 mg/kg is recommended to promote growth performance and enhance antioxidant and immune parameters in Sobaity juveniles.

Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice

BackgroundMatrix metalloproteinase 12 (MMP12) is a macrophage-secreted protein that is massively upregulated as a pro-inflammatory factor in metabolic and vascular tissues of mice and humans suffering from cardiometabolic diseases (CMDs). However, the molecular mechanisms explaining the contributions of MMP12 to CMDs are still unclear.MethodsWe investigated the impact of MMP12 deficiency on CMDs in a mouse model that mimics human disease by simultaneously developing adipose tissue inflammation, insulin resistance, and atherosclerosis. To this end, we generated and characterized low-density lipoprotein receptor (Ldlr)/Mmp12-double knockout (DKO) mice fed a high-fat sucrose- and cholesterol-enriched diet for 16–20 weeks.ResultsDKO mice showed lower cholesterol and plasma glucose concentrations and improved insulin sensitivity compared with LdlrKO mice. Untargeted proteomic analyses of epididymal white adipose tissue revealed that inflammation- and fibrosis-related pathways were downregulated in DKO mice. In addition, genetic deletion of MMP12 led to alterations in immune cell composition and a reduction in plasma monocyte chemoattractant protein-1 in peripheral blood which indicated decreased low-grade systemic inflammation. Aortic en face analyses and staining of aortic valve sections demonstrated reduced atherosclerotic plaque size and collagen content, which was paralleled by an improved relaxation pattern and endothelial function of the aortic rings and more elastic aortic sections in DKO compared to LdlrKO mice. Shotgun proteomics revealed upregulation of anti-inflammatory and atheroprotective markers in the aortas of DKO mice, further supporting our data. In humans, MMP12 serum concentrations were only weakly associated with clinical and laboratory indicators of CMDs.ConclusionWe conclude that the genetic deletion of MMP12 ameliorates obesity-induced low-grade inflammation, white adipose tissue dysfunction, biomechanical properties of the aorta, and the development of atherosclerosis. Therefore, therapeutic strategies targeting MMP12 may represent a promising approach to combat CMDs.

Chromium propionate in turkeys: effects on insulin sensitivity

The objective of this study was to evaluate the effects of dietary chromium (Cr), as Cr propionate (Cr Prop), on measures of insulin sensitivity in turkeys. Plasma glucose and nonesterified fatty acid (NEFA), and liver glycogen concentrations were used as indicators of insulin sensitivity. One-day-old Nicholas Large White female poults (n=336) were randomly assigned to dietary treatments consisting of 0 (control), 0.2, 0.4, or 0.6 mg supplemental Cr/kg diet. Each treatment consisted of 12 replicate cages with 7 turkeys per cage. Final BW were taken on d 34, and on d 35 two birds from each cage were sampled for plasma glucose and NEFA, and liver glycogen determination at the initiation (fed state) and termination (fasted state) of a 24-h fast. Following a 24-h fast, 2 turkeys per cage were refed (refed state) their treatment diet for 4 h, and then harvested. Feed/gain and ADG did not differ between control and Cr-supplemented turkeys over the 34-d study, but feed intake tended (P=0.071) to be greater for controls than turkeys receiving 0.4 mg Cr/kg diet. Fed turkeys had greater plasma glucose (P=0.002) and liver glycogen (P=0.001) concentrations, and lower (P=0.001) NEFA concentrations than fasted birds. Turkeys refed after fasting had greater (P=0.001) plasma glucose and liver glycogen concentrations, and lower (P=0.001) plasma NEFA levels than fed turkeys. Liver glycogen and plasma NEFA concentrations did not differ among control and Cr-supplemented birds in the fed, fasted, or refed state. Plasma glucose concentrations were not affected by treatment in fed or fasted turkeys. Turkeys supplemented with 0.2 or 0.4 mg Cr/kg and refed after fasting had lower (quadratic, P=0.038) plasma glucose concentrations than controls. Plasma glucose concentrations in refed birds did not differ among Cr-supplemented turkeys. The lower plasma glucose concentration in Cr-supplemented turkeys following refeeding is consistent with Cr enhancing insulin sensitivity.

Bioprinted 3D Bionic Scaffolds with Pancreatic Islets as a New Therapy for Type 1 Diabetes-Analysis of the Results of Preclinical Studies on a Mouse Model.

Recently, tissue engineering, including 3D bioprinting of the pancreas, has acquired clinical significance and has become an outstanding potential method of customized treatment for type 1 diabetes mellitus. The study aimed to evaluate the function of 3D-bioprinted pancreatic petals with pancreatic islets in the murine model. A total of 60 NOD-SCID (Nonobese diabetic/severe combined immunodeficiency) mice were used in the study and divided into three groups: control group; IsletTx (porcine islets transplanted under the renal capsule); and 3D bioprint (3D-bioprinted pancreatic petals with islets transplanted under the skin, on dorsal muscles). Glucose, C-peptide concentrations, and histological analyses were performed. In the obtained results, significantly lower mean fasting glucose levels (mg/dL) were observed both in a 3D-bioprint group and in a group with islets transplanted under the renal capsule when compared with untreated animals. Differences were observed in all control points: 7th, 14th, and 28th days post-transplantation (129, 119, 118 vs. 140, 139, 140; p < 0.001). Glucose levels were lower on the 14th and 28th days in a group with bioprinted petals compared to the group with islets transplanted under the renal capsule. Immunohistochemical staining indicated the presence of secreted insulin-living pancreatic islets and neovascularization within 3D-bioprinted pancreatic petals after transplantation. In conclusion, bioprinted bionic petals significantly lowered plasma glucose concentration in studied model species.

Effects of faba bean, blue lupin and rapeseed meal supplementation on amino acid metabolism of dairy cows fed grass silage-based diets.

Information about the amino acid (AA) supply of locally produced protein supplements to dairy cow metabolism is needed to design sustainable diets for milk production. In this dairy cow experiment, grass silage and cereal-based diets supplemented with isonitrogenous amounts of rapeseed meal (RSM), faba beans (FB) and blue lupin seeds (BL) were compared with a control diet (CON) without protein supplementation. The diets were arranged as a 4×4 Latin Square using periods of 21days, and four rumen-cannulated Nordic Red dairy cows were used in the experiment. The intake of all AAs increased in response to protein supplementation and was for many individual AAs higher when RSM rather than the grain legumes FB and BL were fed. The total AA flow at the omasal canal was 3026, 3371, 3373 and 3045g/day for cows fed CON, RSM, FB and BL, respectively, but only RSM resulted in higher milk protein output. This may be explained by the higher provision of essential AA for milk protein synthesis when RSM was fed. The cows fed FB showed some positive features such as a tendency for greater omasal flow of branched-chain AA compared with BL. Overall, low plasma methionine and/or glucose concentrations in all treatments suggest that their supply was possibly limiting further production responses under the dietary conditions of the current study. It seems that the benefits of grain legume supplementation are limited when high-quality grass silage and cereal-based diets are used as the basal diet, but higher responses in amino acid supply and subsequent production responses can be expected when RSM is used.

Hypoglycemia awareness and its associated risk factors, in non-insulin-dependent diabetes in Hail region, Saudi Arabia.

Hypoglycemia is one of the avoidable complications of diabetes mellitus type 1 or 2, which occurs in between 24% to 60% of diabetic patients. It is a state of low plasma glucose concentration, either with or without symptoms, that can expose the patient to risks. Hypoglycemia is associated with impaired brain function, cardiovascular and visual effects, and increased mortality. This study was conducted to assess the knowledge of hypoglycemia as a complication of diabetes mellitus type 2 and the awareness of risk factors among the Hail City population, Kingdom of Saudi Arabia. We conducted a cross-sectional study targeting diabetic patients with type 2 in Hail province from April to August 2022. We used an online questionnaire distributed through popular social media, which included questions on age group, gender, BMI, social status, occupation, education, and income. Approximately 48.2% of patients had episodes of hypoglycemia in the previous three months, while 43% did not have hypoglycemic episodes. Among patients, 424 (73.7%) had less than three hypoglycemic episodes during the previous three months, and 121 (21%) had 3-6 episodes. Hypoglycemic episodes among diabetic patients have critical effects on the patient and may lead them to avoid diabetic drugs, causing hyperglycemia.

Association between Arterial Hypertension and Laboratory Markers, Body Composition, Obstructive Sleep Apnea and Autonomic Parameters in Obese Patients.

Systemic arterial hypertension (SAH) is a multifactorial disease, highly prevalent and associated with health risks. The purpose of this study was to investigate the association between SAH and laboratory, anthropometric, heart rate variability (HRV), and obstructive sleep apnea markers and, secondarily, to analyze the sensitivity and specificity of the variables that are independent factors in the association. Cross-sectional study with 95 obese patients treated at an obesity referral clinic in Salvador, BA, Brazil. SAH data were obtained from electronic medical records. The sample was stratified in the Normotensive Group (NG) and the Hypertensive Group (HG), and laboratory markers, body composition, polysomnography, and HRV were measured to evaluate the association of SAH with the predictor variables. For the analysis, p<0.05 was adopted. The average age of the NG was 36.3 ± 10.1 and HG 40.4 ± 10.6 years; 73.7% were women in the NG and 57.9% in HG; 82.4% in HG had insulin resistance. In the multivarious logistics regression model with adjustments in age, sex, height, and oxyhemoglobin saturation, SAH was inversely associated with fasting plasma glucose mg/dL (odds ratio [OR] = 0.96; 95% confidence interval [CI] = 0.92-0.99) and visceral fat area (VFA) cm2(OR = 0.98; 95% CI = 0.97-0.99). The area under the VFA curve was 0.728; CI 95% (0.620-0.836); fasting plasma glucose 0.693;CI 95% (0.582-0.804). Lower VFA and fasting plasma glucose concentrations were inversely associated with SAH. In addition, fasting plasma glucose and VFA showed a high sensitivity for SAH screening.

Postprandial Metabolic Responses to High-fat Feeding in Healthy Adults Following Ingestion of Oolong Tea–Derived Polymerized Polyphenols: A Randomized, Double-blinded, Placebo-controlled Crossover Study

BackgroundPolymerized polyphenols (PP) found in oolong tea can inhibit pancreatic lipase activity in vitro, and pilot work indicates that this may reduce postprandial lipemia. Since tea contains caffeine and catechins, the interactions between these ingredients and PP warrant investigation. ObjectivesTo assess whether PP ingested alone or with caffeine and catechins lowers postprandial lipemia. MethodsFifty healthy adults [mean (SD) age: 26 (7) y; BMI (in kg/m2): 24.0 (2.7); female: n = 16] completed 4 oral lipid tolerance tests in a placebo-controlled randomized, crossover design. Participants ingested 40 g of fat with either 1) placebo, 2) 100 mg PP, 3) 150 mg PP, or 4) 100 mg PP plus 50 mg caffeine and 63 mg catechins (PP + CC). Blood was sampled for 3 h postprandially to assess concentrations of serum and plasma triacylglycerol and plasma markers of lipid (NEFA; glycerol; LDL and HDL cholesterol; and ApoA-I, A-II, B, C-II, C-III, and E) and glucose metabolism (glucose, insulin, and C-peptide). ResultsSerum and plasma triacylglycerol concentrations and lipid metabolism variables generally increased following any test drink ingestion (main effect of time, p < 0.001). Nevertheless, for the lipid metabolism responses, there were no statistically significant condition–time interactions and no statistically significant differences in incremental or total area under the curve between conditions, apart from HDL cholesterol (p = 0.021). Ingesting 100 mg PP + CC lowered peak plasma glucose, insulin, and C-peptide concentrations compared with all other conditions 30 min postingestion (p < 0.001), with persistent alterations in glucose concentrations observed for 90 min compared with placebo and 100 mg PP conditions. ConclusionsPP ingested at doses ≤150 mg does not clearly alter early-phase postprandial triacylglycerol concentrations in healthy adults, irrespective of the presence or absence of caffeine and catechins. Nevertheless, caffeine and catechins added to PP lowered postprandial glucose and insulin concentrations.This trial was registered in ClinicalTrials.gov as NCT03324191 (https://clinicaltrials.gov/ct2/show/NCT03324191).

Maternal Dietary Carbohydrate Restriction and Mild-to-Moderate Exercise during Pregnancy Modify Aspects of Fetal Development in Rats

To determine whether acute bouts of exercise during pregnancy would predispose the fetus to increased risk if maternal dietary carbohydrate were restricted, untrained pregnant rats were randomly assigned to a 0% (low), 12% (moderate) or 60% (high) glucose diet, and either rested or exercised daily for 20 min from d 16 to term on a rodent treadmill at a mild (15.5 m/min) or moderate (24.3 m/min) intensity. A 3 ՠ3 nested factorial model with and without food intake as a covariate was employed. Both greater exercise intensity and the lower levels of dietary carbohydrate independently decreased term maternal liver and plantaris glycogen concentrations and increased plasma lactate concentrations. However, significant differences due to exercise disappeared (except for plasma lactate) with food intake controlled for in the model, indicating that energy deficits modulated these exercise effects. In contrast, for the offspring, when food intake was controlled for, a restricted level of maternal dietary carbohydrate significantly lowered fetal weight, plasma glucose and insulin concentrations and liver glycogen concentrations measured at term. Exercise alone did not reduce mean fetal weight if nested weights within a litter were used in the statistical analysis. Mild to moderate maternal exercise lowered only fetal plasma glucose concentrations and only if maternal food intake was not controlled for. These results indicate that acute exercise during pregnancy can have detrimental effects on fetal development only if dietary glucose is severely restricted. Otherwise, adequate glucose and energy in the maternal diet in untrained pregnant rats during repeated bouts of acute exercise seem to protect the fetus.

Low Dose Fructose Ingestion during Gestation and Lactation Affects Carbohydrate Metabolism in Rat Dams and Their Offspring

This study examined whether drinking fructose or glucose water with a balanced diet affects pregnant and lactating rats and their offspring. The animals were divided into three groups and drank tap water, 100 g/L fructose water or 100 g/L glucose water. The fructose-fed dams ate significantly more food but drank less water than the glucose-fed group. On d 19 of pregnancy, the fructose-fed dams had significantly heavier livers and significantly higher plasma glucose and insulin concentrations than dams consuming tap water. Five days after litters were weaned, dams fed fructose had the heaviest body weights, significantly higher plasma glucose concentration compared with the group receiving tap water and significantly higher plasma triglyceride concentration compared with the glucose-fed group. Weanlings of the fructose-fed dams had significantly lower plasma glucose concentration but a significantly higher plasma insulin concentration than the weanlings of the group receiving tap water. These findings suggest that intake of fructose during gestation can cause hyperglycemia and hyperinsulinemia in dams and, at weaning, greater weight gain in dams and hyperinsulinemia in offspring. These abnormalities in dams and weanlings could be the result of insulin resistance.

Dietary Methionine Restriction Alleviates Hyperglycemia in Pigs with Intrauterine Growth Restriction by Enhancing Hepatic Protein Kinase B Signaling and Glycogen Synthesis

BackgroundIndividuals with intrauterine growth restriction (IUGR) are prone to developing type 2 diabetes mellitus (T2DM). Dietary methionine restriction (MR) improves insulin sensitivity and glucose homeostasis in individuals with normal birth weight (NBW). ObjectiveThis study investigated the effects of MR on plasma glucose concentration and hepatic and muscle glucose metabolism in pigs with IUGR. MethodsThirty female NBW and 60 same-sex spontaneous IUGR piglets (Landrace × Yorkshire) were selected. After weaning (day 21), the piglets were fed diets with adequate methionine (NBW-CON and IUGR-CON) or 30% less methionine (IUGR-MR) (n = 6). At day 180, 1 pig with a body weight near the mean of each replication was selected for biochemical analysis. ResultsThe IUGR-CON group showed 41.6%, 68.6%, and 67.1% higher plasma glucose concentration, hepatic phosphoenolpyruvate carboxykinase activity, and glucose-6-phosphatase activity, respectively, than the NBW-CON group (P < 0.05). Muscle glycogen content and glycogen synthase activity were 36.9% and 38.8% lower, respectively, in the IUGR-CON than the NBW-CON group (P < 0.05), respectively, and there was decreased hepatic and muscle protein kinase B phosphorylation in the IUGR-CON group (P < 0.05). Compared with the IUGR-CON pigs, the IUGR-MR pigs had 28.7% lower plasma glucose concentrations (P < 0.05), which were similar to those of the NBW-CON pigs (P ≥ 0.05). The hepatic glycogen content and glycogen synthase activity of the IUGR-MR pigs were 62.9% and 50.8% higher than those of the IUGR-CON pigs (P < 0.05) and 53.5% and 84.3% higher than the NBW-CON pigs (P < 0.05), respectively. The IUGR-MR pigs’ hepatic and muscle protein kinase B phosphorylation was higher than that of the IUGR-CON pigs (P < 0.05) and similar to that of the NBW-CON pigs (P ≥ 0.05). ConclusionsMR attenuates hyperglycemia in IUGR pigs by enhancing hepatic protein kinase B signaling and glycogen synthesis, implying a potential nutritional strategy to prevent type 2 diabetes mellitus in IUGR offspring.

Glucagon in health and diabetes

Abstract For decades all attention focused on the hormone insulin as a key player in diabetes and the role of glucagon was less studied or understood. We now know that both these pancreatic hormones play a critical role in maintaining glucose homeostasis in the body and the secretion of one controls the secretion of the other in an inverse relationship as described by the bihormonal theory of Unger. Glucagon, secreted by the α-cells of the islets of pancreas is a key hormone that has a “hyperglycemic” effect and is secreted in response to low plasma glucose concentration. Besides hypoglycemia, glucagon release is also stimulated by prolonged fasting or starvation, exercise as well as consumption of protein-rich meals. It is regulated by several key endocrine and paracrine mechanisms and the autonomic system in response to various stimuli including nutrient intake through various complex neurohormonal factors. It primarily increases endogenous hepatic glucose production, stimulates lipid and protein catabolism, and plays a key role in appetite regulation and increasing energy expenditure. Therefore, glucagon functions as a counter-regulatory hormone to insulin stimulating hepatic glycogenolysis, gluconeogenesis, fatty acid oxidation, and ketogenesis. With mounting evidence, there has been a paradigm shift in the management of diabetes following the advent of new agents that address different pathophysiological mechanisms contributing to worsening hyperglycemia. Targeting the alpha-cell defect and consequent glucagon hypersecretion has therefore emerged as an important therapeutic strategy in type 2 diabetes mellitus (T2DM) management as well as body weight management. The currently available medications, including glucagon-like peptide 1 (GLP-1) receptor agonists, DPP-4 inhibitors, and amylin mimics (pramlintide), essentially focus on lowering glucagon levels and correcting this critical pathophysiological component in the multifactorial T2DM management strategies.

Caloric restriction alters galanin and its receptor in hypothalamus of wistar rats

Caloric restriction (CR) reverses obesity and insulin resistance, yet the detailed mechanism underlying its beneficial effects is poorly understood. The galanin system is closely associated with energy metabolism. It is yet unclear whether this effect of CR is operating through the regulation of the galanin system. To test this effect, we subjected rats to either 60% or 40% calorie restriction for one week. After the one-week's experiment, galanin and many genes associated with the function of metabolism were examined. The present findings showed that 7 days of 60% or 40% calorie restriction lowered body weight and plasma glucose concentration in rats, suggesting that rats under CR have improved weight loss and systemic glucose metabolism. Besides, the lower plasma glucose was associated with an increase in muscle glucose uptake resulting from elevations of both glucose transporter 4 (GLUT4) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression in skeletal muscles. Moreover, the levels of galanin and its receptors (GALR1-3) mRNA markedly increased in the hypothalamus of CR rats. Taken together, these results supported that non-pharmacological activation of the galanin/GALR signaling with CR regimen led to activation of the PGC-1α/GLUT4 axis in skeletal muscles which can enhance energy metabolism. The current findings provide additional evidence that galanin is a critical factor for CR-induced weight loss and metabolic changes. CR regimen may be recognized as a non-pharmacological intervention that could prevent obesity and its associated metabolic disorders.

Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health.

IntroductionWhile oral glucose ingestion typically leads to a decrease in circulating glucagon levels, a substantial number of persons display stable or rising glucagon concentrations when assessed by radioimmunoassay (RIA). However, these assays show cross-reactivity to other proglucagon cleavage products. Recently, more specific assays became available, therefore we systematically assessed glucagon and other proglucagon cleavage products and their relation to metabolic health.Research Design and MethodsWe used samples from 52 oral glucose tolerance tests (OGTT) that were randomly selected from persons with different categories of glucose tolerance in an extensively phenotyped study cohort.ResultsGlucagon concentrations quantified with RIA were non-suppressed at 2 hours of the OGTT in 36% of the samples. Non-suppressors showed lower fasting glucagon levels compared to suppressors (p=0.011). Similar to RIA measurements, ELISA-derived fasting glucagon was lower in non-suppressors (p<0.001). Glucagon 1-61 as well as glicentin and GLP-1 kinetics were significantly different between suppressors and non-suppressors (p=0.004, p=0.002, p=0.008 respectively) with higher concentrations of all three hormones in non-suppressors. Levels of insulin, C-peptide, and free fatty acids were comparable between groups. Non-suppressors were leaner and had lower plasma glucose concentrations (p=0.03 and p=0.047, respectively). Despite comparable liver fat content and insulin sensitivity (p≥0.3), they had lower 2-hour post-challenge glucose (p=0.01).ConclusionsGlucagon 1-61, glicentin and GLP-1 partially account for RIA-derived glucagon measurements due to cross-reactivity of the assay. However, this contribution is small, since the investigated proglucagon cleavage products contribute less than 10% to the variation in RIA measured glucagon. Altered glucagon levels and higher post-challenge incretins are associated with a healthier metabolic phenotype.

Acute Effects of Kawakawa (Piper excelsum) Intake on Postprandial Glycemic and Insulinaemic Response in a Healthy Population.

Background: Piper excelsum (kawakawa) is an endemic shrub of Aotearoa, New Zealand, of cultural and medicinal importance to Māori. Its fruits and leaves are often consumed. These tissues contain several compounds that have been shown to be biologically active and which may underpin its putative health-promoting effects. The current study investigates whether kawakawa tea can modulate postprandial glucose metabolism. Methods: We report a pilot three-arm randomized crossover study to assess the bioavailability of kawakawa tea (BOKA-T) in six male participants with each arm having an acute intervention of kawakawa tea (4 g/250 mL water; 1 g/250 mL water; water) and a follow-up two-arm randomized crossover study to assess the impact of acute kawakawa tea ingestion on postprandial glucose metabolism in healthy human volunteers (TOAST) (4 g/250 mL water; and water; n = 30 (15 male and 15 female)). Participants consumed 250 mL of kawakawa tea or water control within each study prior to consuming a high-glycemic breakfast. Pre- and postprandial plasma glucose and insulin concentrations were measured, and the Matsuda index was calculated to measure insulin sensitivity. Results: In the BOKA-T study, lower plasma glucose (p < 0.01) and insulin (p < 0.01) concentrations at 60 min were observed after consumption of a high-dose kawakawa tea in comparison to low-dose or water. In the TOAST study, only plasma insulin (p = 0.01) was lower at 60 min in the high-dose kawakawa group compared to the control group. Both studies showed a trend towards higher insulin sensitivity in the high-dose kawakawa group compared to water only. Conclusions: Consuming kawakawa tea may modulate postprandial glucose metabolism. Further investigations with a longer-term intervention study are warranted.

BIOCHEMICAL IMPLICATIONS OF ORAL ADMINISTRATION OF EXTRACTS OF Acalypha wilkesiana LEAVES IN RABBITS

Thus, this study was conducted to evaluate the biochemical implications of oral administration of extracts of Acalypha wilkesiana leaves, using some serum parameters, in normal experimental rabbits. A total of eighteen (18) rabbits were randomized into three groups (A, B and C) of six animals each and treated with aqueous (A) and ethanol (B) extracts of Acalypha wilkesiana leaves. The extracts were administered orally at a dose of 300mg/kg body weight for a period of twenty-one (21) days. Group C animals served as control.Data are represented as Mean ± S.E.M (n = 6). Significance of Difference was tested by ANOVA at P &lt; 0.05.Administration of the aqueous or ethanol extract, at a dose of 300 mg/kg body weight, to normal rabbits resulted in a significantly (P &lt; 0.05) lower plasma glucose concentration. Treatment with the aqueous or ethanol extract resulted in a non-significantly (P &gt; 0.05) higher serum albumin, HDL-cholesterol and a non-significantly (P &gt; 0.05) lower serum total protein, globulin, triglycerides, LDL-cholesterol, as compared with the control, in normal rabbits. However, treatment with the ethanol extract resulted in a non-significantly (P &gt; 0.05) higher total cholesterol, while treatment with the aqueous extract resulted in a non-significantly (P &gt; 0.05) lower total cholesterol of the normal rabbits, as compared with the control. This shows that, the aqueous or ethanol extracts have hypoglycaemic and hypocholesterolemic effects on the rabbits.